Optically active 1-aryl-2-fluoro-substituted ethylamines, which are the subject of the present invention, are useful as important intermediates for medicines and agricultural chemicals. For example, a thrombin inhibitor having a racemic 1-aryl-2-fluoro-substituted ethylamine structure in its partial skeleton are being under development (Patent Publication 1). The optically active 1-aryl-2-fluoro-substituted ethylamines and their production method have become particularly important with the establishment of the concept of a chiral drug, by which, when there exist optical isomers, drug developments proceed with using either one of the optical isomers required.
The optically active 1-aryl-2-fluoro-substituted ethylamines of the present invention are novel materials, so that there are no reports made on their production method.
As prior art relevant to the present invention, there are reports about: (1) a method of synthesizing a para-methoxyphenyl (PMP) protected racemic 1-aryl-2-fluorosubstituted ethylamine by reaction of N-(4-methoxy phenyl)-N-2,2-difluoroethylidene)amine and an aryl lithium compound (Patent Publication 1); (2) a method of synthesizing an acetyl protected racemic 1-aryl-2-fluoro-substituted ethylamine by desililation and fluorination of an alkenyl trimethylsilane (Non-patent Publication 1) and (3) a method of synthesizing a hydrochloride of optically active 1-phenyl-2,2,2-trifluoroethylamine of the formula [18] by hydrogenolysis of a hydrochloride of optically active secondary amine of the formula [17] in the presence of a palladium catalyst
[Chem. 1]
[where * represents an asymmetric carbon][Chem. 2]
[where * represents an asymmetric carbon].
Patent Publication 1: PCT 02/50056
Non-patent Publication 1: J. Org. Chem., (U.K.), 2001, pp. 233-234
Non-patent Publication 2: J. Org. Chem., (U.S.), 1977, Vol. 42, No. 14, pp. 2436-2439